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Evidence-based medicine and research regarding posterior circulation
ischemia (PCI) has consistently lagged behind anterior circulation
ischemia (ACI) due to presumed diminished prevalence of the disease and
surgical inaccessibility. However, posterior circulation infarcts
account for roughly one-quarter of all ischemic strokes,1 and
they remain a significant cause of patient morbidity and mortality. In
this article, we review pertinent vertebrobasilar anatomy, along with
background research of posterior circulation atherosclerotic pathology.
Further, we illustrate case examples of vertebrobasilar disease,
highlighting endovascular treatment options.

Background

The clinical diagnosis of vertebrobasilar insufficiency (VBI) and PCI
is generally more complex than that of ACI, especially for a
non-neurologist. Whereas aphasia and weakness associated with ACI is
typically obvious, VBI and PCI present with symptomatology that can be
somewhat more subtle. Typical findings are vague and may be confused
with inner ear disease. Based on the New England Medical
Center-Posterior Circulation Registry (NEMC-PCR),2 the most
common symptoms include dizziness and syncope (47%), unilateral limb
weakness (41%), dysarthria (31%), headache (28%), and nausea or vomiting
(27%). The most frequent signs are unilateral limb weakness (38%), gait
ataxia (31%), unilateral limb ataxia (30%), dysarthria (28%), and
nystagmus (24%). Fewer than 1% of patients with VBI presented with only
one complaint, signifying pattern recognition in diagnosis of such
patients. In general, a combination of cranial nerve palsies and long
tract signs localizes the lesion to the brain stem and should,
therefore, trigger a posterior circulation vascular evaluation.

For many years, patients with suspected ACI have been interrogated
and treated with a vastly different approach than patients with
suspected PCI. Although researchers have questioned this double standard
in the 1980s and 1990s, it was not until 2004 when Caplan et al
drastically changed this paradigm by demonstrating that stroke
mechanisms responsible for PCI and ACI were more alike than previously
thought.3 In their study of 407 patients from the NEMC-PCR,
data collected from 1988 to 1996 demonstrated that cardiogenic emboli
(24% vs. 38%) were less common than large artery occlusive disease (32%
vs. 9%) in PCI compared to ACI, respectively. The difference in the
cardiogenic embolism rate was explained by the fact that the posterior
circulation receives approximately one-fifth of the total brain
circulation, leading to fewer emboli based on this hemodynamic
phenomenon. Thus, by factoring in this inherent hemodynamic disparity,
the researchers concluded that the pathophysiology of PCI is indeed very
similar to ACI. This landmark trial signified that just like ACI, PCI
should also be evaluated thoroughly to select an appropriate therapy
based on the causative stroke mechanism.

With respect to vascular imaging, noninvasive angiography was not
widely available until the 1990s. Prior to that, catheter angiography of
the vertebrobasilar system was performed infrequently due to the
inherent risk associated with this procedure, specifically the
infarction risk of vital brainstem structures. Therefore, while the
anterior circulation was investigated frequently and thoroughly,
angiography of the vertebrobasilar circulation was only performed in
severe clinical cases, contributing to more uncertainty regarding PCI.4

It was generally believed that PCI had low recurrence and mortality
rates, making primary and secondary prevention ineffective at a
population level. The small recurrence rate was based upon multiple
small scaled studies performed in the 1960s and 1970s, which
demonstrated recurrence rates of 2%-6%.5 It was not until
1998 that the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID)
trial demonstrated a PCI stroke recurrence rate of 22% (15% per year)
during a 14-month mean follow-up of 59 symptomatic patients with more
than 50% stenosis in the intracranial posterior circulation.6 In 2003, Qureshi et al retrospectively studied 102 patients diagnosed with symptomatic vertebrobasilar stenosis.7
Over a mean follow-up of 15 months, 14% (11% per year) had a recurrent
stroke with a total mortality of 21%. In the same year, a meta-analysis
of 36 cohorts from 46 articles demonstrated that the recurrence event
rate of PCI was not lower than the recurrence rate of ACI;
interestingly, it raised the possibility that this rate might be even
higher in the first month following a posterior circulation event.5 A prospective study in 2009 supported this theory by showing a 30% recurrence rate for PCI.8 These recurrence rates were significantly higher than previously thought, igniting new interest in this topic.

Multiple treatment options have been available for ACI with the
mainstay of treatment including carotid endarterectomy (CEA) and
anticoagulation for noncardioembolic and cardioembolic strokes,
respectively. The single treatment option for PCI was traditionally
anticoagulation, since surgical intervention is technically challenging
due to difficult access to the posterior circulation. In contrast, the
cervical carotid arteries are surgically accessible with the first
reported case of CEA published in 1954.9 Anticoagulation
therapy for PCI was primarily based on a few uncontrolled retrospective
studies performed in the 1950s and 1960s.10,11 While multiple
randomized and controlled trials in early the 1990s showed the
effectiveness of anticoagulation therapy for recurrent PCI of
cardioembolic etiology, there was no clear advantage of warfarin therapy
for PCI due to noncardioembolic causes, which led to further clumping
of these various stroke mechanisms into one group.12-15 This
practice was further validated by a retrospective study in 1995 that
demonstrated superiority of warfarin over aspirin, even in PCI due to
intracranial stenosis.16 In 2001, however, the
Warfarin–Aspirin Recurrent Stroke Study (WARSS), a randomized,
double-blind, multicenter clinical trial, showed equal efficacy of these
2 treatments for noncardioembolic PCI.17 In 2005, the WASID
investigation also indicated equal efficacy of warfarin vs. aspirin for
preventing strokes due to intracranial atherosclerosis.18
Since both ACI and PCI were included in this trial, in 2006, subgroup
analysis of the PCI patients was published indicating no significant
difference in recurrent stroke rates between the two therapies.19
The trial was terminated prematurely due significantly higher rates of
adverse effects in the warfarin-treated arm than the
antiplatelet-treated arm. Therefore, empiric anticoagulation therapy not
only failed to demonstrate increased efficacy in the setting of
noncardiogenic phenomenon, but it also was shown to carry a worse
adverse effects profile.

With growing research and acceptance of coronary artery stenting for
treating coronary artery disease, coupled with the advancing knowledge
and techniques of carotid artery stenting (CAS), there was a natural
outgrowth of potential endovascular treatment options for PCI in the
setting of vertebral and basilar artery atherosclerotic disease. While
numerous randomized trials have shown effectiveness of CEA and CAS, no
same scaled trial for PCI has been conducted. In 2009, it was shown that
there is a higher percentage of 50% or more stenosis in PCI versus ACI
patients (26% vs. 11.5), which in concert with a high recurrence rate in
PCI, demanded endovascular consideration.20 However, in 2007
the Carotid and Vertebral Artery Transluminal Angioplasty Study
(CAVATAS) subgroup analysis failed to show any advantage of endovascular
therapy over medical management for proximal vertebral artery stenosis.21
The study was nevertheless underpowered with only 8 patients in each
arm. In 2012, a meta-analysis revealed very low complication rates for
endovascular treatment of proximal vertebral artery stenosis (stroke and
death rate of 1.1%).22 A restenosis rate of 23% with almost
half requiring repeat interventions was also reported. In 2013, it was
shown that intracranial vertebrobasilar (VB) stenosis carried a much
higher 90-day recurrent event rate than extracranial VB stenosis (33%
vs. 16%).23 Therefore, endovascular treatment of intracranial
VB stenosis needed to be evaluated. The SAMMPRIS trial, however, had
already been terminated due to unexpectedly very high rates of strokes
in the endovascular treatment arm of the study compared to the medical
arm.24 At that point, the FDA restricted the use of the
particular stent to patients with 70%-99% stenosis and 2 or more strokes
despite maximized medical therapy. In asymptomatic patients, studies
have shown no significant difference in stroke rates with or without
vertebral artery stenosis.25

Anatomy and Vertebrobasilar Imaging Considerations

The vertebral arteries (VAs) are the first superoposterior branch of
the subclavian arteries and are divided into 4 anatomic segments. These
paired arteries course medially and posteriorly between the longus colli
and anterior scalene muscles (V1, preforaminal or extraosseous segment)
and travel superiorly through the foramina transversaria, most commonly
from C6 to C2 (V2, foraminal segment). The VAs exit the transverse
foramina of the axis and course around the lateral masses of the atlas
(V3, extraspinal segment), and
finally pierce the dura at the atlantoccipital space and ascend
superiorly through the foramen magnum (V4, intradural or intracranial
segment). At the pontomedullary junction, the two VAs unite to form a
nonpaired basilar artery, which courses cephalad and divides into the
posterior cerebral arteries (PCAs) at the pontomesencephalic junction
or, more accurately, in the interpeduncular cistern.26

The major branches of the vertebrobasilar system can be divided into
perforant and circumferential arteries. The posterior inferior
cerebellar arteries (PICAs), anterior inferior cerebellar arteries
(AICAs) and superior cerebellar arteries (SCAs) are the lateral
circumferential arteries. The perforant branches directly supply the
brainstem and are typically not seen on imaging due to their small
caliber. Medial circumferential arteries fill in the gap between the 2
mentioned territories.

The VAs typically measure 3-5 mm; however, there is significant variability in terms of size.27
The left VA is dominant in half of the population. Right dominant and
codominant VAs each compose 25% of the population. It has been reported
that 15% of individuals have an atretic (< 2 mm) VA. The VAs are
typically the first superior branch of the subclavian arteries.
Occasionally, they may be the second branch, if the thyrocervical trunk
branches more proximally as the first superior branch. On the right
side, the thyroidea ima artery may occasionally arise as the first
superior branch of the subclavian artery. In 6% of cases, the left VA
may originate directly from the aortic arch, between the left common
carotid artery (CCA) and left subclavian artery origins. This particular
variation represents the second most common aortic arch anomaly,
following the common origin of the innominate and left common carotid
arteries, commonly but incorrectly referred to as a bovine arch.28
The VAs may enter the foramina transversaria at levels other than C6 in
10% of cases. Occasionally, only one VA is the sole contributor of the
basilar artery with the other VA terminating as PICA. Duplications and
other rare aberrant origins have also been reported in the literature.29

The initial work-up for VBI and PCI typically starts with a
nonenhanced CT (NECT), which is an excellent modality for detecting
various intracranial pathologies. However, ischemic stroke remains a
clinical diagnosis, and NECT should not be used to diagnose such an
entity due to a low sensitivity of 31% and 81% at 3 and 5 hours,
respectively. The sensitivities are even lower in PCI due to inherent
artifact associated with the posterior fossa, primarily due to streak
artifact from adjacent osseous structures. The primary goal of NECT is
to exclude intracranial hemorrhage and other stroke mimics. Confirmation
of ischemic stroke on NECT is a secondary goal, and a normal
examination does not exclude ischemia. MRI is superior in detecting
ischemia. Diffusion-weighted imaging (DWI) has sensitivity of at least
90% and could aid in diagnosis.

Ultrasound examination is of limited utility in the evaluating the
posterior circulation, predominantly due to lack of an acoustic window.
Although the most common location of atherosclerosis of VAs is at their
origin, only the V2 segments of the VAs are routinely evaluated.
Direction of blood flow is easily determined with color Doppler, which
is crucial in diagnosis of subclavian steal syndrome. In this syndrome,
there is critical stenosis of the subvclavian artery proximal to origin
of the VA with reversal of blood flow in the ipsilateral VA perfusing
the upper extremity vasculature. In short, the vertebral artery steals
blood from the cerebral circulation to supply the upper extremity.
Spectral Doppler waveforms only show changes in severe cases of
stenosis. A normal VA waveform is a low-resistant arterial waveform.
Spectral broadening, high-resistant waveform and elevated peak systolic
velocities may indicate stenosis; however, these findings are not
sensitive enough, and no criteria resembling carotid stenosis have been
established for staging VA stenosis.

CT angiography (CTA) and MR angiography (MRA) are the 2 most common
imaging techniques for evaluating cerebral vasculature. In comparison to
CTA, MRA has no ionizing radiation and may be performed without
intravenous contrast by using time-of-flight (TOF) sequences. This is
especially important in patients with chronic kidney disease where
intravenous contrast is problematic. TOF sequences provide excellent
images of the circle of Willis. Imaging the cervical carotid and
vertebral arteries with this technique is somewhat limited due to a
large field of view, and the V1 segments of VAs are typically not seen.
Complete evaluation of the vasculature may be accomplished with CTA or
contrast-enhanced MRA. CTA is quick and widely accessible. Ionizing
radiation and iodinated contrast are the downsides of this modality.
Although CTA and MRA techniques have vastly improved from the early
days, artifacts are associated with both of these modalities. Therefore,
catheter angiography remains the gold standard for imaging the cerebral
vasculature. Figure 1 demonstrates all 4 segments of the vertebral
arteries and the basilar artery by CTA; postprocessed image demonstrates
the underlying bony anatomy of the head and neck.

The goal of each imaging modality is to clearly demonstrate each
segment of the posterior circulation, separating normal from diseased
sections. The clinical use of ultrasound, CTA, and MRA, as well as
cerebral angiography are further illustrated in the following cases.

Representative Cases

Case 1. Vertebral Osteal Disease

A 67-year-old man with past medical history (PMH) significant for
hypertension and chronic kidney disease presented with one month of
intermittent vertigo, dizziness, light-headedness, blurry vision, double
vision, headache and unsteadiness. On admission, noncontrast head CT
and brain MRI demonstrated subacute infarcts in the bilateral cerebellar
hemispheres, a subacute to chronic infarct in the left frontal lobe,
and left temporal lobe encephalomalacia (Figure 2). MRA was significant
for occlusion of the proximal segment of the right vertebral artery and
critical stenosis of the left vertebral artery at the ostium (Figures
3A, 4A, 4B). Digital subtraction angiogram (DSA) performed on hospital
day 6 demonstrated critical stenosis of the left vertebral artery ostium
(Figure 4C). The right vertebral artery was occluded with poor
collateral flow to the V4 segment (Figure 3B). The right vertebral
artery supplied some flow to the right PICA territory but no flow was
seen distally.

The patient was started on anticoagulation therapy with aspirin and
clopidogrel. Two days later, on hospital day 8, the left vertebral
artery was treated with angioplasty and stented using a 4-x-18-mm
bare-metal stent (VISION stent; Abbott Laboratories, Abbott Park,
Illinois). Postintervention angiogram demonstrated no residual stenosis
and no significant stent encroachment within the left subclavian artery
(Figure 4D). There was excellent runoff to the basilar artery with new
retrograde flow within V4 and V3 segments. The postprocedure hospital
course was otherwise uneventful and the patient was discharged on
aspirin and clopidogrel. He continued to do well postprocedure without
posterior circulation insufficiency symptomatology.

Initial head CT and brain MRI demonstrated several areas of subacute
infarction in the right cerebellum, bilateral pons, left thalamus, and
portions of the right occipital lobe (Figures 5, 6). The right vertebral
artery was densely calcified on CT and demonstrated abnormal signal on
MRI, concerning for occlusion MRA demonstrated occlusion of the right
vertebral artery and critical stenosis of the V4 segment of the left
vertebral artery (Figure 7A). There was stenosis of the basilar artery,
nonvisualization of the PCAs and multiple areas of stenosis in the
intracranial ICAs and MCAs. Diagnostic DSA confirmed the areas of
stenosis seen on MRA but did show some flow in the right vertebral
artery (Figures 7B, C). The appearance of the basilar artery on DSA
raised concern for thrombosis of the stenotic vessel and treatment with
aspirin and clopidigrel was initiated. MRA and CTA performed after 13
days of anticoagulation demonstrated improved flow to the right
vertebral artery and basilar artery (Figure 8). There was persistent
severe stenosis of the distal intracranial portions of both vertebral
arteries and mild stenosis of the mid basilar artery. The next day,
stent-supported angioplasty of the mid right vertebral artery stenosis
was performed using a 4.5-x-20-mm Gateway balloon-Wingspan stent system
(Boston Scientific, Fremont, California). Postprocedure angiography
demonstrated approximately 50% residual narrowing at the level of the
stenosis with markedly improved luminal diameter and flow (Figure 9).
The patient continued to do well clinically, maintained on an
anti-platelet regimen.

Case 3. Mid-basilar Stenosis

A 58-year-old man with PMH significant for hypertension, diabetes,
and hyperlipidemia was admitted for altered mental status. An unenhanced
CT (not shown) demonstrated no acute finding. US revealed findings
consistent with stenosis of the right vertebral artery (Figure 10). MRI
performed the same day revealed multiple areas of restricted diffusion
in the occipital lobes, compatible with ischemic strokes of embolic
etiology (Figure 11). Old lacunar infarcts in the cerebellum were also
evident. MRA of the brain suggested at least a 70% stenosis of the mid
basilar artery, which was upgraded to 90% stenosis upon DSA (Figure 12).
Since the patient had experienced multiple strokes despite aggressive
medical management, endovascular management of the mid-basilar artery
stenosis was considered. On day 9 of admission, successful angioplasty
was performed (Figure 13). Following intervention, the patient remained
stable with no additional episodic posterior circulation ischemic
episodes or stroke.

Conclusion

Primary atherosclerotic disease of the vertebrobasilar system remains
a significant subset of ischemic vascular disease and stroke affecting
the population-at-large. With increasing clinical awareness,
investigators have advanced noninvasive imaging capabilities, which
primarily affect the vertebral and/or basilar arteries, and precisely
diagnose areas of pathology. Concomitant neurointerventional advances in
catheter-based therapies have advanced the treatment options for this
often debilitating or deadly disease. Continued research remains
paramount in an effort to recognize symptomatology, perform appropriate
medical imaging tests, and formulate appropriate treatment plans.

The effect of low-dose warfarin on the risk of stroke in patients
with nonrheumatic atrial fibrillation. The Boston Area Anticoagulation
Trial for Atrial Fibrillation Investigators. New Engl J Med
1990;323(22):1505-1511.